Non-psychoactive multi-cannabinoid and polysaccharide and polysaccharopeptide-based therapeutic compositions and methods of their administratio

Abstract

A fixed dose combination formulation drug comprised of up to five cannabinoids, namely cannabidiol, cannabichromene, cannabidiolic acid, cannbidovorin, and cannabigerol, one or more mushroom biomasses of Coroilus versicolor or Trametes versicolor or their respective active peptides, polysaccharides, or polysaccharidopeptides, and optionally of up to three terpenes, namely alpha-terpinene, bisabolol, and camphene, in an orally available pharmaceutical carrier, for the alleviation of the adverse effects of cancer chemotherapy agents, including adverse effects on the gastrointestinal tract, the chemoreceptor trigger zone, and the peripheral nervous system, and that shows activity adjunctively against ovarian cancer, particularly ovarian cancer that is therapeutically platinum-resistant or platinum-sensitive, as well as method of their manufacture, and methods of their therapeutic administration to a patient.

What is claimed is: 
     
         1 . A pharmaceutical drug formulation for administration to a patient in need thereof, comprising one or more cannabinols selected from the group consisting of:
 (a) cannabidiol and the pharmaceutically acceptable salts, esters, solvates, enaqntiomers, optical isomers, diastereomers, and geometric isomers thereof, present in a molar concentration of from 0.03M to 3.0M;   (b) cannabigerol and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.006M to 0.6M; or   (c) cannabichromene and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.006M to 0.6M;   (d) cannabidiolic acid and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.006M to 0.6M;   (e) cannabidovorin and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.006M to 0.6M;   
       and one or more non-cannabinol constituents selected from the group consisting of:
 (f) bisabolol and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.021M to 2.1M; 
 (g) camphene and the pharmaceutically acceptable salts, esters, solvates, optical isomers, and geometric isomers thereof, present in a molar concentration of from 0.022M to 2.2M; or 
 (h) one or more mushroom biomasses selected from the mushroom species  Coriolus versicolor  or  Trametes versicolor.    
 
     
     
         2 . The pharmaceutical formulation as claimed in claim  20 , wherein cannabidiol is present in a molar concentration of 0.3M. 
     
     
         3 . The pharmaceutical formulation as claimed in claim  20 , wherein cannabigerol is present in a molar concentration of 0.06M. 
     
     
         4 . The pharmaceutical formulation as claimed in claim  20 , wherein cannabichromene is present in a molar concentration of 0.06M. 
     
     
         5 . The pharmaceutical formulation as claimed in claim  20 , wherein cannabidiolic acid is present in a molar concentration of 0.06M. 
     
     
         6 . The pharmaceutical formulation as claimed in claim  20 , wherein cannabidivorin is present in a molar concentration of 0.06M. 
     
     
         7 . The pharmaceutical formulation as claimed in claim  20 , wherein bisabolol is present in a molar concentration of 0.21M. 
     
     
         8 . The pharmaceutical formulation as claimed in claim  20 , wherein camphene is present in a molar concentration of 0.22M. 
     
     
         9 . The pharmaceutical formulation as claimed in claim  20 , additionally comprising one or more compositions selected from monk fruit extract present in a concentration ranging from 0.0025% to 0.25% w/w and ginger essential oil present in a concentration ranging from 0.059% to 5.9% w/w. 
     
     
         10 . The pharmaceutical formulation as claimed in claim  28 , wherein said monk fruit extract is present in a concentration of 0.025% w/w. 
     
     
         11 . The pharmaceutical formulation as claimed in claim  28 , where said ginger essential oil is present in a concentration of 0.59% w/w. 
     
     
         12 . The formulation as claimed in claim  20 , wherein said cannabinol is selected from the group additionally comprising cannabidiol monomethyl ether (CBDM), cannabidiol-C4 (CBD-C4), cannabidiorcol (CBD-C1), Δ 9 -tetrahydrocannabinol (Δ 9 -THC), Δ 9 -tetrahydrocannabinolic acid (Δ 9 -THCA), Δ 9 -tetrahydrocannabivarin (Δ 9 -THCV), Δ 9 -THCVA, Δ 8 -THC, Δ 8 -THCA, Δ 8 -THCV, Δ 8 -THCVA, iso-tetrahydrocannabinol-type (iso-THC), cannabinol (CBN), cannabinolic acid (CBNA), cannabinol-C4 (CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinol methyl ether (CBNM), cannabinodiol (CBND), cannabigerovarin (CBGV), cannabigerolic acid (CBGA), cannabigerovarinic acid (CBGVA), cannabigerol monomethyl ether (CBGM), cannabigerolic acid monomethyl ether (CBGAM), cannabichromene (CBC), cannabichromenic acid (CBCA), cannabichromevarin (CBCV), cannabichromevarinic acid (CBCVA), cannabichromanon (CBCN), cannabicyclol (CBL), cannabicyclolic acid (CBLA), cannabicyclovarin (CBLV), cannabivarin (CBV), cannabivarinic acid (CBVA), cannabielsoin (CBE), cannabielsoic acid A (CBEA-A), cannabielsoic acid B (CBEA-B), cannabitriol (CBT), cannabitriolvarin (CBTV), ethoxy-cannabitiolvarin (CBTVE), cannabifuran (CBF), dehydrocannabifuran (DCBF), cannabiripsol (CBR), an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof, or a mixture thereof. 
     
     
         13 . The formulation as claimed in claim  20 , wherein at least one of said mushroom species is  Coriolus versicolor.    
     
     
         14 . The formulation as claimed in claim  20 , wherein at least one of said mushroom species is  Trametes versicolor.    
     
     
         15 . The formulation as claimed in claim  20 , wherein said mushroom biomass comprises one or more polysaccharides. 
     
     
         16 . The formulation as claimed in claim  34 , wherein one of said polysaccharides comprises a homoglycan. 
     
     
         17 . The formulation as claimed in claim  34 , wherein one of said polysaccharides comprises one or more beta-glucans. 
     
     
         18 . The formulation as claimed in claim  36 , wherein said beta-glucans are characterized in having β-linked interchain linkages. 
     
     
         19 . The formulation as claimed in claim  36 , wherein said beta-glucans are selected from the group comprising polymers of D-glucose. 
     
     
         20 . The formulation as claimed in claim  38 , wherein said polymers of D-glucose are comprised of monomers that are optionally and independently substituted with one or more of hydrogen, a gluccuronic acid, arabinose, mannose, fucose, galactose, or xylose. 
     
     
         21 . The formulation as claimed in claim  36 , wherein said beta glucans are selected from the group consisting of polysaccharide Krestin, polysaccharopeptide, or musarin. 
     
     
         22 . The formulation of claim  40 , wherein said polysaccharopeptide is polysaccharopeptide-1. 
     
     
         23 . The formulation of claim  41 , wherein said polysaccharopeptide-1 is polysaccharopeptide-1a. 
     
     
         24 . The formulation of claim  41 , wherein said polysaccharopeptide-1 is polysaccharopeptide-1b. 
     
     
         25 . The formulation of claim  41 , wherein said polysaccharopeptide-1 is polysaccharopeptide-1c. 
     
     
         26 . The formulation of claim  41 , wherein said polysaccharopeptide-1 is polysaccharopeptide-1d. 
     
     
         27 . The formulation of claim  41 , wherein said polysaccharopeptide-1 is polysaccharopeptide-1e. 
     
     
         28 . The formulation of claim  43 , wherein said polysaccharopeptide-1b is polysaccharide-1b1. 
     
     
         29 . The formulation of claim  40 , wherein said polysaccharopeptide is polysaccharopeptide-2. 
     
     
         30 . The formulation of claim  40 , wherein said polysaccharopeptide is polysaccharopeptide-3. 
     
     
         31 . The formulation of claim  40 , wherein said polysaccharide Krestin is a beta-glucan comprising a β-1,4 main chain and optionally and independently substituted by β-1,3 and β-1,6 side chains. 
     
     
         32 . The formulation of  claim 20 , wherein said mushroom species  Trametes versicolor  is a biomass comprising polysaccharide Krestin. 
     
     
         33 . The formulation of claim  51 , wherein said polysaccharide Krestin comprises beta-glucan polymers, having a molecular weight of approximately 100 Kda. 
     
     
         34 . The formulation claimed in claim  51 , wherein said polysaccharide Krestin comprises monomers that are optionally and independently substituted by a peptide. 
     
     
         35 . The formulation of  claim 20 , wherein said mushroom species independently comprise one or more of polysaccharopeptide, polysaccharide Krestin, or musarin. 
     
     
         36 . The formulation of claim  41 , wherein said musarin is a peptide having a molecular weight of approximately 12 kDa. 
     
     
         37 . A method of manufacturing a pharmaceutical formulation as claimed in  claim 20 , said method of manufacturing comprising the steps of:
 (a) combining at least one medium chain triglyceride oil with full spectrum hemp distillate, one or more cannabinols selected from cannabigerol isolate, and cannabichromene distillate in a cooking vessel;   (b) heating the combined compositions of step (a) until a temperature of from 140 degrees F. to 200 degrees F. has been reached;   (c) cooling the product of step (b) to room temperature; and   (d) adding a mushroom biomass and mixing until homogenized.   
     
     
         38 . The method of  claim 12 , comprising the additional step of adding monk fruit extract to said heated mixture before said cooling begins. 
     
     
         39 . The method of  claim 12 , comprising the additional step of adding ginger essential oil to said cooled mixture. 
     
     
         40 . A method of treating an animal or human patient in need thereof to alleviate the adverse side effects of cancer chemotherapy, comprising the step of administering a pharmacologically sufficient amount of a formulation as claimed in  claim 20 . 
     
     
         41 . The method as claimed in claim  59 , wherein said patient is being treated for a disease selected from the group consisting of cancer therapeutic-induced gastrointestinal adverse effects, cancer therapeutic-induced peripheral neuropathy, drug-resistant cancer, or drug-sensitive cancer. 
     
     
         42 . The method as claimed in claim  60 , wherein said drug-resistant cancer is ovarian cancer.